Nearly Half of ICDs in Massachusetts Placed for Off – Label Indications

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.

NEW ORLEANS – Nearly half of patients who received an implantable cardioverter defibrillator in Massachusetts during 1998-2008 had at least one clinical factor that categorized them as an off-label recipient, based on the exclusion criteria used in the clinical trials that established the efficacy of these devices.

The most common off-label use occurred in patients aged either 75 or older or 19 or younger, which in both cases put them outside of the age enrollment criteria for the implantable cardioverter defibrillator (ICD) trials, Dr. Norman S. Kato reported while presenting a poster at the annual meeting of the American College of Cardiology.

ICDs given to patients outside the age range that was tested in trials accounted for well over a quarter of all ICD use in Massachusetts during the period studied, and more than half of all off-label use. Other common off-label ICD uses occurred in patients with renal insufficiency or a recent acute MI, reported Dr. Kato, a cardiothoracic surgeon in Encino, Calif., who has consulted with the Food and Drug Administration, and his associates in their poster (J. Am Coll. Cardiol. 2011;57:E184).

Their analysis, which included 15,724 ICD recipients during the 11-year period studied, represents "the first analysis [of ICD use] to encompass all patients who have received this technology in a single state," he said in an interview. But he also cautioned that "it would be incorrect to generalize these results to other states, or to assume anything about practice patterns in Massachusetts" in the years following 2008.

"The key finding from our study was that patients over age 65 represent a significant portion of the population receiving these devices. Our research revealed that about 45% of all patients receiving the devices in the Medicare age group were age 75 or older." In addition, the results showed that 15% of recipients were age 85 or older.

"ICDs may have been implanted when there was little empirical evidence to support their use. Because subjects over age 75 were specifically excluded from the randomized clinical trials [of ICDs,] there is no scientific evidence to support the notion that ICDs are safe or effective in this group," Dr. Kato said. "We really need to conduct randomized clinical trials in the excluded groups to determine safety and efficacy. If there is a lot of off-label use for a specific indication, then it stands to reason that clinical trials should be conducted to determine the safety and efficacy of the device for these specific indications.

"Off-label use does not necessarily mean that the use was without benefit or was unsafe," he noted. "Off-label use is simply the use of the device for conditions that were not tested during the randomized clinical trials."

The Centers for Medicare and Medicaid Services, in a 2005 decision memo on ICD use, noted that only 10% of patients who were enrolled in the two largest ICD trials were aged 75 or older, and as a consequence "the implantation of a defibrillator in the most elderly patients should be carefully considered and not routinely recommended," the memo said (CAG-00157R3).

Dr. Kato’s study of Massachusetts ICD usage also showed disproportionate placement of ICDs in men. During 1998-2008, men received ICDs three- to eightfold more often than did women for primary prevention indications, and three- to ninefold more often for secondary prevention.

These findings raise issues of a sex bias or a disease bias that favored men over women for ICD placement, he said. "In general, men have a higher risk for and greater rates of heart attack and coronary artery disease than women, hence men should probably be more likely to receive an ICD. But this merits consideration since results from other studies have also identified the same frequency differences by gender," said Dr. Kato.

The analyses used data compiled by the Massachusetts Department of Health and Human Services on hospital case mix and charge, as well as population estimates from the National Center for Health Statistics.

During the 11-year period studied, the rate of off-label ICD use for primary prevention indications ranged from 28% to 50%, depending on the year. In 2008, about 45% of Massachusetts patients who received an ICD had at least one off-label clinical feature, with age being an off-label factor for about 28% of all recipients. Primary-prevention use, which totaled 13,801 patients over the 11 years studied, occurred in patients with a diagnosis of heart failure or cardiomyopathy.

In 2008, about 45% of patients who received an ICD for secondary prevention had an off-label feature. Secondary-prevention use, which occurred in a total of 1,923 patients in the 11 years studied, included the indications of a history of cardiac arrest or ventricular arrhythmia during the year prior to ICD placement in patients who did not have a primary-prevention indication.

Criteria that led to exclusion from the ICD efficacy trials and hence constitute markers of off-label use included patients undergoing simultaneous percutaneous coronary intervention or coronary artery bypass surgery, and patients with a recent acute MI, renal failure, liver failure, neurologic failure, solid tumor, or dementia, as well as patients on dialysis, and patients aged 75 or older or aged 19 or younger.

Dr. Kato and his associates on the study said that they had no disclosures.